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Non-muscle-invasive bladder cancer; NMIBC; Transurethral resection; Intravesical therapy; Recurrence; Surveillance; Urinary biomarkers

Introduction

Bladder cancer is one of the most commonly diagnosed malignancies worldwide, with non-muscle-invasive bladder cancer (NMIBC) accounting for approximately 75% of cases at initial presentation [1]. NMIBC is confined to the urothelium or lamina propria and is characterized by a high risk of recurrence and potential for progression to muscle-invasive disease. Effective management requires a combination of tumor resection, risk-adapted intravesical therapy, and long-term surveillance to optimize oncological outcomes while minimizing treatment-related morbidity. Transurethral resection of the bladder tumor (TURBT) serves as the cornerstone of NMIBC treatment, allowing for both diagnosis and initial tumor removal. However, due to the high recurrence rate, adjuvant intravesical therapies such as Bacillus Calmette-Guérin (BCG) or chemotherapy are often recommended based on the patient's risk stratification. While BCG remains the gold standard for intermediate- and high-risk NMIBC, ongoing challenges such as supply shortages and treatment resistance necessitate alternative therapeutic approaches, including novel immunotherapies and targeted agents [2].

Surveillance is a critical component of NMIBC management, as early detection of recurrence can significantly improve patient outcomes. Current guidelines recommend routine cystoscopy and urinary cytology, though the integration of urinary biomarkers and advanced imaging modalities may enhance diagnostic accuracy and reduce the burden of invasive procedures. Despite these advancements, challenges remain in optimizing treatment selection, improving patient adherence to surveillance protocols, and mitigating disease progression. This review explores the current landscape of NMIBC treatment and surveillance, discussing the efficacy of various therapeutic strategies, challenges in long-term disease management, and emerging innovations aimed at improving patient outcomes [3].

Discussion

The management of non-muscle-invasive bladder cancer (NMIBC) remains a complex and evolving challenge due to its high recurrence rates and potential for progression. Despite advancements in treatment and surveillance, several key issues continue to shape clinical decision-making, including optimizing therapeutic efficacy, addressing treatment resistance, refining risk stratification, and improving long-term patient outcomes [4].

Efficacy and Limitations of Current Treatments

Transurethral resection of the bladder tumor (TURBT) remains the primary intervention for NMIBC, providing both diagnostic and therapeutic benefits. However, incomplete resection or the presence of residual microscopic disease can contribute to recurrence. Repeat TURBT is often recommended for high-risk cases to improve staging accuracy and ensure complete tumor removal. Intravesical therapies, particularly Bacillus Calmette-Guérin (BCG), play a crucial role in reducing recurrence and delaying progression in intermediate- and high-risk NMIBC. Despite its proven efficacy, BCG therapy is associated with local and systemic side effects, and prolonged shortages have limited its availability. Alternative intravesical agents, such as mitomycin C, gemcitabine, and valrubicin, have been explored as substitutes, with varying degrees of success. Novel immunotherapies and checkpoint inhibitors are also being investigated for patients who fail BCG therapy [5].

Challenges in Risk Stratification and Personalized Treatment

Accurate risk stratification is essential for guiding NMIBC management, yet existing classification systems have limitations in predicting disease progression. Current guidelines categorize patients into low-, intermediate-, and high-risk groups based on tumor grade, size, multiplicity, and presence of carcinoma in situ (CIS). However, the heterogeneity of NMIBC suggests that more precise molecular and genomic biomarkers could enhance risk assessment and facilitate personalized treatment strategies. Emerging research into genetic mutations, tumor microenvironment characteristics, and immune response markers may help refine patient selection for specific therapies. The integration of artificial intelligence (AI) and machine learning into predictive modeling could further improve individualized risk assessment and treatment planning [6].

Surveillance Strategies: Balancing Sensitivity and Patient Burden

Given the high recurrence rates associated with NMIBC, rigorous surveillance is necessary to detect early signs of disease recurrence or progression. Cystoscopy remains the gold standard for monitoring, but its invasiveness, cost, and patient discomfort highlight the need for improved non-invasive alternatives [7]. Urinary biomarkers, such as NMP22, UroVysion, and cytokeratin-based assays, have demonstrated potential in supplementing traditional surveillance methods. While these biomarkers offer increased sensitivity, their specificity remains a concern, leading to potential false-positive results. Advances in next-generation sequencing and liquid biopsy techniques may enhance the reliability of non-invasive monitoring [8].

Emerging Therapeutic Innovations and Future Directions

With ongoing challenges in NMIBC management, several novel therapeutic approaches are being investigated. Immunotherapy, particularly immune checkpoint inhibitors targeting PD-1/PD-L1 pathways, has shown promise in BCG-unresponsive disease [9]. Additionally, gene therapy, intravesical viral vectors, and antibody-drug conjugates represent potential avenues for enhancing treatment efficacy. Photodynamic therapy (PDT), radiofrequency ablation, and device-assisted drug delivery methods, such as thermochemotherapy, are also being explored to improve drug penetration and tumor targeting. As these modalities undergo further clinical evaluation, their integration into NMIBC treatment guidelines may provide additional options for patients who fail conventional therapies [10].

Conclusion

Optimizing the treatment and surveillance of NMIBC requires a multifaceted approach that incorporates improved risk stratification, novel therapeutic strategies, and enhanced surveillance techniques. While TURBT and intravesical therapy remain the foundation of treatment, emerging therapies and non-invasive monitoring tools offer promising avenues for improving long-term outcomes. Future research should focus on personalized treatment approaches, refining surveillance protocols, and overcoming limitations associated with current therapies to ensure more effective disease management and better quality of life for NMIBC patients.

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